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PubMed | Capital Medical University, Chinese National Institute for Radiological Protection, Peking University, Henan Institute of Occupational Medicine and Peking Union Medical College
Type: | Journal: Mutation research. Genetic toxicology and environmental mutagenesis | Year: 2014

The present study aims to evaluate the use of the fluorescence in situ hybridization (FISH) translocation assay for retrospective dose estimation of acute accidental exposure to radiation in the past. Reciprocal translocation analysis by FISH with three whole-chromosome probes was performed on normal peripheral blood samples. Samples were irradiated with 0-5Gy (60)Co -rays in vitro, and dose-effect curves were established. FISH-based translocation analyses for six accident victims were then performed, and biological doses were estimated retrospectively by comparison with the dose-effect curves. Reconstructed doses by FISH were compared with estimated doses obtained by analysis of di-centrics performed soon after exposure, or with dose estimates from tooth-enamel electron paramagnetic resonance (EPR) data obtained at the same time as the FISH analysis. Follow-up FISH analyses for an adolescent victim were performed. Results showed that dose-effect curves established in the present study follow a linear-quadratic model, regardless of the background translocation frequency. Estimated doses according to two dose-effect curves for all six victims were similar. FISH dose estimations of three adult victims exposed to accidental radiation less than a decade prior to analysis (3, 6, or 7 years ago) were consistent with those estimated with tooth-enamel EPR measurements or analyses of di-centrics. Estimated doses of two other adult victims exposed to radiation over a decade prior to analysis (16 or 33 years ago) were underestimated and two to three times lower than the values obtained from analysis of di-centrics or tooth-enamel EPR. Follow-up analyses of the adolescent victim showed that doses estimated by FISH analysis decrease rapidly over time. Therefore, the accuracy of dose estimates by FISH is acceptable only when analysis is performed less than 7 years after exposure. Measurements carried out more than a decade after exposure through FISH analysis resulted in underestimation of the biological doses compared with values obtained through analysis of di-centrics and tooth-enamel EPR.

PubMed | Chinese National Institute for Radiological Protection and Henan Institute of Occupational Medicine
Type: | Journal: Mutation research. Genetic toxicology and environmental mutagenesis | Year: 2014

The present study aims to measure chromosomal aberrations and micronuclei in peripheral blood lymphocytes from 25 subjects exposed to 0.10-0.33 Gy external or internal irradiation 32-41 years ago using conventional cytogenetic analysis methods. The frequencies of total chromosome-type aberrations and micronucleus significantly increased in the exposed group compared with that in age-matched control group (p<0.001); chromatid-type aberrations showed no difference between the two groups (p>0.05). When exposed subjects were divided into two groups based on exposure dose, higher levels of dicentric plus translocation frequencies were observed in the 0.15 Gy dose group compared with those in the <0.15 Gy dose group, though the difference was not significant. Borderline association between exposure dose and dicentric frequency was detected in the exposed group (r=0.358; p=0.079). These results suggest that the genotoxic effects of ionizing radiation remain in subjects exposed to low-dose radiation even decades after exposure.

PubMed | Centers for Disease Control and Prevention, Texas Tech University, Sun Yat Sen University, National Institute for Occupational Health and Poison Control and Henan Institute of Occupational Medicine
Type: Journal Article | Journal: Archives of toxicology | Year: 2016

Recently, diesel engine exhaust (DEE) was reclassified as a known carcinogen to humans. DNA methylation alterations in DNA damage response (DDR)-related genes have the potential to affect DEE exposure-related cancer risk. However, the evidence regarding the association between DEE exposure and methylation alterations in DDR-related genes is limited. In 117 DEE-exposed workers and 112 non-DEE-exposed workers, we measured urinary concentrations of six mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs). We also determined the methylation levels of three DDR-related genes (p16, RASSF1A, and MGMT) and LINE-1 by bisulfite-pyrosequencing assay. We found that DEE-exposed workers exhibited significantly lower mean promoter methylation levels of p16, RASSF1A, and MGMT than non-DEE-exposed workers (all p<0.001). In all study subjects and non-smoking workers, increasing quartiles of urinary summed OH-PAHs was associated with hypomethylation of p16, RASSF1A, and MGMT (all p<0.05). In non-smoking workers, methylation in p16, RASSF1A, and MGMT decreased by 0.36% [95% confidential interval (CI): -0.60, -0.11%], 0.46% (95% CI: -0.79, -0.14%), and 0.55% (95% CI: -0.95, -0.15%), respectively, in association with highest versus lowest quartile of urinary summed OH-PAHs. In addition, p16, RASSF1A, MGMT, and LINE-1 methylation levels showed negative correlations with cytokinesis-block micronucleus cytome index which was previously measured in the same workers (all p<0.05). In conclusion, our results clearly indicated that DEE exposure and increased genetic damage were associated with hypomethylation of p16, RASSF1A, and MGMT. Future studies with larger sample size are needed to confirm these associations.

PubMed | Weifang Medical University, Centers for Disease Control and Prevention, Sun Yat Sen University, National Institute for Occupational Health and Poison Control and 2 more.
Type: Journal Article | Journal: Occupational and environmental medicine | Year: 2016

Diesel engine exhaust (DEE) is a ubiquitous environmental pollutant and is carcinogenic to humans. To seek early and sensitive biomarkers for prediction of adverse health effects, we analysed the components of DEE particles, and examined the genetic and oxidative damages in DEE-exposed workers.101 male diesel engine testing workers who were constantly exposed to DEE and 106 matched controls were enrolled in the present study. The components of DEE were analysed, including fine particulate matter (PM2.5), element carbon (EC), nitrogen dioxide (NO2), sulfur dioxide (SO2) and polycyclic aromatic hydrocarbons (PAHs). Postshift urine samples were collected and analysed for 1-hydroxypyrene (1-OHP), an internal exposure marker for DEE. Levels of DNA strand breaks and oxidised purines, defined as formamidopyrimidine-DNA glycosylase (FPG) sites in leucocytes, were measured by medium throughput Comet assay. Urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) was also used to determine the level of oxidative stress.We found higher levels of PM2.5, EC, NO2, SO2 and PAHs in the diesel engine testing workshop and significantly higher urinary 1-OHP concentrations in exposed subjects (p<0.001). Compared with controls, the levels of parameters in normal Comet and FPG-Comet assay were all significantly higher in DEE-exposed workers (p<0.001), and in a dose-dependent and time-dependent manner. There were no significant differences between DEE-exposed workers and controls in regard to leucocyte FPG sensitive sites and urinary 8-OHdG levels.These findings suggest that DEE exposure mainly induces DNA damage, which might be used as an early biomarker for risk assessment of DEE exposure.

Zhang X.,National Institute for Occupational Health and Poison Control | Duan H.,National Institute for Occupational Health and Poison Control | Gao F.,Sun Yat Sen University | Li Y.,Sun Yat Sen University | And 5 more authors.
Toxicological Sciences | Year: 2015

The International Agency for Research on Cancer has recently reclassified diesel engine exhaust (DEE) as a Group 1 carcinogen. Micronucleus (MN), nucleoplasmic bridge (NPB), and nuclear bud (NBUD) frequencies in peripheral blood lymphocytes (PBLs) are associated with cancer risk. However, the impact of DEE exposure on MN frequency has not been thoroughly elucidated due to mixed exposure and its impact on NPB and NBUD frequencies has never been explored in humans. We recruited 117 diesel engine testing workers with exclusive exposure to DEE and 112 non-DEE-exposed workers, and then we measured urinary levels of 4 mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) using high-performance liquid chromatography-mass spectrometry as well as MN, NPB, and NBUD frequencies in PBLs using cytokinesis-block MN assay. The DEE-exposed workers exhibited significantly higher MN, NPB, and NBUD frequencies than the non-DEE-exposed workers (P<0.05). Among all study subjects, increasing levels of all 4 urinary OH-PAHs, on both quartile and continuous scales, were associated with increased MN, NPB, and NBUD frequencies (all P<0.05). When the associations were analyzed separately in DEE-exposed and non-DEE-exposed workers, we found that the association between increasing quartiles of urinary 9-hydroxyphenanthrene (9-OHPh) and MN frequencies persisted in DEE-exposed workers (P=0.001). The percent of MN frequencies increased, on average, by 23.99% (95% confidential interval, 9.64-39.93) per 1-unit increase in ln-transformed 9-OHPh. Our results clearly show that exposure to DEE can induce increases in MN, NPB, and NBUD frequencies in PBLs and suggest that DEE exposure level is associated with MN frequencies. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.

PubMed | Zhengzhou University and Henan Institute of Occupational Medicine
Type: Letter | Journal: Biomedical and environmental sciences : BES | Year: 2014

This study examined ionizing radiation-induced tumor necrosis factor (ligand) superfamily, member 4 (TNFSF4) mRNA expression changes in human peripheral blood cells and their distribution in a normal population. The results showed that expression level of TNFSF4 mRNA exhibited a dose-dependent response after different irradiation doses, but that was independent of incubation time post-irradiation. Moreover, it was not affected by age and gender in 51 healthy donors. Our studies indicate that TNFSF4 can be considered as a candidate gene to develop a new biodosimeter.

PubMed | Zhengzhou University and Henan Institute of Occupational Medicine
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2014

Using quantitative real-time polymerase chain reaction (PCR) array, we explored and compared the expression changes of inflammation-related genes in human peripheral blood irradiated with 0.5, 3, and 10 Gy doses of X-rays 24 h after exposure. Results indicated that the expression of 62 out of 84 genes was significantly altered after X-ray radiation. Among these 62 genes, 35 (such as TNFSF4) are known to be associated with radiation response, but others are novel. At a low radiation dose (0.5 Gy), 9 genes were up-regulated and 19 were down-regulated. With further increased dose to 3 Gy, 8 unique genes were up-regulated and 19 genes were down-regulated. We also identified 48 different genes that were differentially expressed significantly after 10 Gy of irradiation, and among these transcripts, up-regulated genes accounted for only one-third (16 genes) of the total. Of the 62 genes, 31 were significantly altered only at a specific dose, and a total of 10 genes were significantly expressed at all 3 doses. The dose- and time-dependent expression of CCL2 was confirmed by quantitative real-time reverse-transcription PCR. A number of candidate genes reported herein may be useful molecular biomarkers of radiation exposure in human peripheral blood.

Qin W.H.,Henan Institute of Occupational Medicine
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases | Year: 2012

To determined hydrogen selenide in workplace air with atomic fluorescence. Hydrogen selenide were sampled with 0.1 mol/L sodium hydroxide solution in multi-hole absorbing tubes. The sampled absorbing solution were digested with (9+1) nitric acid/perchloric acid. The selenide in sample were reduced by potassium borohydride in 5.0% hydrochloride solution and determined with atomic fluorescence. There was a good linearity (r=0.9999) over the concentration of 0-150 microg/L, The precision of low, middle and high concentration were 3.1%, 7.4% and 6.7%, respectively. The sample collection rate can reach 99%. The method was accurate and sensitive to detect hydrogen selenide in workplace air.

PubMed | Henan Institute of Occupational Medicine
Type: Journal Article | Journal: Biomedical and environmental sciences : BES | Year: 2014

To investigate the distribution of mitochondria DNA 4 977 bp deletion, a common deletion (CD), in normal populations of Chinese, human peripheral blood samples from sixty healthy donors were collected, and levels of the CD in genomic DNA from the samples were detected using real-time PCR. The results showed that the CD was found in 27 health donors, with its positive rate being 45% (27/60). The CD ratio was between 0 and 0.00308%, and not affected by age and gender in sixty healthy donors. Our studies indicate that the CD ratio is low, and do not show the age-dependent accumulation and any gender difference in peripheral whole blood from the normal Chinese population.

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